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Genetic susceptibility to tuberculosis in Africans: a genome-wide scan

Lookup NU author(s): Dr Richard Bellamy, Professor Matthew Collin, David Wilkinson

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Abstract

Human genetic variation is an important determinant of the outcome of infection with Mycobacterium tuberculosis. We have conducted a two-stage genome-wide linkage study to search for regions of the human genome containing tuberculosis-susceptibility genes. This approach uses sibpair families that contain two full siblings who have both been affected by clinical tuberculosis. For any chromosomal region containing a major tuberculosis-susceptibility gene, affected sibpairs inherit the same parental alleles more often than expected by chance. In the first round of the screen, 299 highly informative genetic markers, spanning the entire human genome, were typed in 92 sibpairs from The Gambia and South Africa. Seven chromosomal regions that showed provisional evidence of coinheritance with clinical tuberculosis were identified. To identify whether any of these regions contained a potential tuberculosis-susceptibility gene, 22 markers from these regions were genotyped in a second set of 81 sibpairs from the same countries. Markers on chromosomes 15q and Xq showed suggestive evidence of linkage (lod = 2.00 and 1.77, respectively) to tuberculosis. The potential identification of susceptibility loci on both chromosomes 15q and Xq was supported by an independent analysis designated common ancestry using microsatellite mapping. These results indicate that genome-wide linkage analysis can contribute to the mapping and identification of major genes for multifactorial infectious diseases of humans. An X chromosome susceptibility gene may contribute to the excess of males with tuberculosis observed in many different populations.


Publication metadata

Author(s): Bellamy R, Beyers N, Keith PW, McAdam KP, Ruwende C, Gie R, Samaai P, Bester D, Meyer M, Corrah T, Collin M, Camidge DR, Wilkinson D, Hoal-van Helden E, Whittle HC, Amos W, van Helden P, Hill AVS

Publication type: Article

Journal: Proceedings of the National Academy of Sciences of the United States

Year: 2000

Volume: 97

Issue: 14

Pages: 8005-8009

ISSN (print): 0027-8424

Publisher: National Academy of Sciences

URL: http://dx.doi.org/10.1073/pnas.140201897

DOI: 10.1073/pnas.140201897

Notes: 0027-8424 Journal Article


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